POS1439 CANCER IN PATIENTS WITH RHEUMATIC DISEASES EXPOSED TO DIFFERENT BIOLOGIC AND TARGETED SYNTHETIC DMARDS IN REAL-WORLD CLINICAL PRACTICE: DATA FROM A MULTICENTER REGISTER
Authors: I. Castrejon, J. Molina Collada, C. Perez-Garcia, P. Vela-Casasempere, C. Diaz-Torne, C. Bohórquez, J. M. Blanco, F. Sánchez-Alonso
Journal: Annals of the Rheumatic Diseases (2022)

Background Extensive evidence has confirmed no increased risk of cancer associated to either conventional synthetic DMARDs or anti-TNF in patients with rheumatic diseases. The risk of cancer in biologic (bDMARDs) different to anti-TNF and targeted synthetic (tsDMARDs) is considerably less investigated. As new therapies are emerging, more data in real-world registries are needed to confirm safety in other treatment groups. Objectives To compare the risk of cancer of tsDMARDs and other bDMARDs versus anti-TNF in patients with rheumatic diseases. Methods Data of patients enrolled in BIOBADASER 3.0 up to October 2021 with the start of any bDMARD or tsDMARD were analyzed. For each group, demographic and clinical variables were estimated. Changes to therapy and occurrence of serious adverse events collected annually. Incident cancer was defined as any cancer during the exposure classified according to Meddra dictionary leading to therapy discontinuation. Incidence rate ratios of cancer per 1000 patients-year (PYs) and 95% confidence interval were estimated. Incidence rate ratio was calculated for each group versus anti-TNF. Results We identified 271 cancers in BIOBADASER 3.0, corresponding to a cancer incident rate of 7.4 (6.5-8.3) per 1000 PY of exposure. Patients exposed to anti-TNF and anti-IL17 were younger, with lower disease duration and comorbidity versus other groups. Proportionally more malignancies were identified in the anti-CTLA-4 group (3.4%) versus the anti-TNF group (2.9%). The rates of incident cancer ranged between 2.6 events/1000 PY in the anti-IL17 group and 15.3 events/1000 PY in the anti-CTLA-4 group. The rate of cancer did not differ significantly in patients exposed to JAKi [0.8 (95% CI 0.4-1.5)], anti CD20 [1.1 (95% CI 0.6-1.8)], or anti-IL6 [1.3 (95% CI 0.9-1.9)] versus anti-TNF; it was significantly lower in patients exposed to anti-Il17 [0.4 (95% CI 0.2-0.9)], and significantly higher in patients exposed to anti-CTLA-4 [2.2 (95% CI 1.4-3.2)]. The most frequent malignancy was non-melanoma skin cancer, followed by solid cancer (mainly breast cancer with 24 events and lung cancer with 14 events) and melanoma (13 events). Table 1. New Cancer Diagnosis Among Patients with anti-TNF versus other therapies Anti-TNF (N=6356 ) JAKi (N=1079 ) Anti-CD20 (N=667 ) Anti-IL6 (N=1178 ) Anti-CTLA-4 (N=783 ) Anti-IL17 (N=1051 ) Female, n (%) 3738 (58.8) 868 (80.4) 523 (78.4) 947 (80.4) 598 (76.4) 492 (46.81) Mean age, (SD) 54.8 (14.7) 58.5 (12.4) 60.9 (13.6) 59.8 (15.1) 64.0 (12.8) 52.2 (11.6) Mean start age, (SD) 49.1 (14.0) 56.6 (12.3) 57.9 (13.5) 55.7 (15.2) 59.7 (13.0) 49.8 (22.2) Disease duration, median (IQR) 6.2[2.2-13.0] 10.4[4.7 -17.2] 11.0[5.1-18.5] 8.3[3.2-15.1] 10.3[5.2-17.0] 3.1[0.3-10.7] Charlton Index 1.9 (1.3) 2.4 (1.6) 2.4 (1.7) 2.4 (1.7) 2.8 (1.9) 1.8 (1.3) First line biologic, n (%) 99 (53.2) 2 (22.2) 1 (7.1) 6 (20.0) 5 (18.5) 2 (66.7) New cancer diagnosis, n (%) 186 (2.9%) 9 (0.8%) 14 (2.1%) 30 (2.5%) 27 (3.4%) 5 (0.5%) Median years of follow-up months 4.2 [2.3-7.3] 2.4 [1.4-3.2] 1.0 [1.0-1.0] 2.6 [1.3-6.6] 4.4 [1.5-5.7] 1.8 [1-5-2.2] Time of exposure, yrs 26233.5 1652.7 1871.5 3196.7 1762.1 1921 Cancer Incidence Rate (per 1000 PY ) ancer Incide 7.1 (6.1-8.2) 5.4 (2.8-10.5) 7.5 (4.4-12.6) 9.4 (6.6-13.4) 15.3 (10.5-22.3) 2.6 (1.1-6.3) .6 (1.1-6.3). 5.2 (4.4-6.1) 6.3 (1.6-8.1) 5.9 (3.3-10.6) 7.5 (5-11.2) 10.8 (6.9-16.9) 1.6 (0.5-4.8) .6 (0.5-4 0.3 (0.2-0.6) 0 (0-0) 1.1 (0.3-4.3) 0.3 (0-2.2) 0.6 (0.1-4) 0 (0-0) (0-0)1-4)3)9)) Rate (per 1.6 (1.2-2.2) 1.8 (0.6-5.6) 0.5 (0.1-3.8) 1.6 (0.7-3.8) 4 (1.9-8.3) 1 (0.3-4.2) Rate ratio (vs anti-TNF ) NA 0.8 (0.4-1.5) 1.1 (0.6-1.8) 1.3 (0.9-1.9) 2.2 (1.4-3.2) 0.4 (0.2-0.9) Conclusion In this register-based study, rates of incident cancer did not differ between patients treated with anti-TNF and other bDMARDs or tsDMARDs, with the possible exception of a potential increased risk in patients treated with anti-CTLA-4. Acknowledgements Thank you to all patients, rheumatologists, and to the research personnel from the Spanish Foundation of Rheumatology who made this study possible. Disclosure of Interests Isabel Castrejon: None declared, Juan Molina Collada: None declared, Carolina Perez-Garcia: None declared, Paloma Vela-Casasempere Speakers bureau: ROCHE, UCB, GSK, LILLY, Consultant of: PFIZER, BMS, LILLY, UCB, GSK, Abbvie, Fresenius Kabi, Grant/research support from: ROCHE, ABBVIE, PFIZER, BMS, LILLY, SANDOZ, AMGEN, Cesar Diaz-Torne: None declared, Cristina Bohórquez: None declared, J M Blanco: None declared, Fernando Sánchez-Alonso: None declared